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Open AccessArticle

Molecular Characterization of Circulating Tumor Cells Enriched by A Microfluidic Platform in Patients with Small-Cell Lung Cancer

1
Molecular Oncology Group, Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
2
Department of Respiratory and Critical Care Medicine, Sozialmedizinisches Zentrum Baumgartner Höhe, Sanatoriumstrasse 2, 1140 Vienna, Austria
3
Division of Oncology, Biomedical Center Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Malá Hora 4C, 036 01 Martin, Slovakia
4
Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 880; https://doi.org/10.3390/cells8080880
Received: 25 June 2019 / Revised: 11 July 2019 / Accepted: 31 July 2019 / Published: 13 August 2019
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Abstract

At initial diagnosis, most patients with small-cell lung cancer (SCLC) present with metastatic disease with a high number of tumor cells (CTCs) circulating in the blood. We analyzed RNA transcripts specific for neuroendocrine and for epithelial cell lineages, and Notch pathway delta-like 3 ligand (DLL3), the actionable target of rovalpituzumab tesirine (Rova-T) in CTC samples. Peripheral blood samples from 48 SCLC patients were processed using the microfluidic Parsortix™ technology to enrich the CTCs. Blood samples from 26 healthy donors processed in the same way served as negative controls. The isolated cells were analyzed for the presence of above-mentioned transcripts using quantitative PCR. In total, 16/51 (31.4%) samples were CTC-positive as determined by the expression of epithelial cell adhesion molecule 1 (EpCAM), cytokeratin 19 (CK19), chromogranin A (CHGA), and/or synaptophysis (SYP). The epithelial cell lineage-specific EpCAM and/or CK19 gene expression was observed in 11 (21.6%) samples, and positivity was not associated with impaired survival. The neuroendocrine cell lineage-specific CHGA and/or SYP were positive in 13 (25.5%) samples, and positivity was associated with poor overall survival. DLL3 transcripts were observed in four (7.8%) SCLC blood samples and DLL3-positivity was similarly associated with poor overall survival (OS). CTCs in SCLC patients can be assessed using epithelial and neuroendocrine cell lineage markers at the molecular level. Thus, the implementation of liquid biopsy may improve the management of lung cancer patients, in terms of a faster diagnosis, patient stratification, and on-treatment therapy monitoring. View Full-Text
Keywords: small-cell lung carcinoma; circulating tumor cells; microfluidics; gene expression analysis; synaptophysin; chromogranin A; rovalpituzumab tesirine small-cell lung carcinoma; circulating tumor cells; microfluidics; gene expression analysis; synaptophysin; chromogranin A; rovalpituzumab tesirine
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Obermayr, E.; Agreiter, C.; Schuster, E.; Fabikan, H.; Weinlinger, C.; Baluchova, K.; Hamilton, G.; Hochmair, M.; Zeillinger, R. Molecular Characterization of Circulating Tumor Cells Enriched by A Microfluidic Platform in Patients with Small-Cell Lung Cancer. Cells 2019, 8, 880.

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